Development of a Conceptual Model of Physical Functioning Limitations Experienced by Patients with Late-Stage Chronic Kidney Disease: A Qualitative Interview Study.

INTRODUCTION: Limitations in physical functioning are common in patients with late-stage chronic kidney disease (CKD) and can greatly affect their lives. Using patient interviews, this study reports experiences associated with physical functioning limitations for patients with late-stage CKD. METHODS: A preliminary conceptual model on concepts relevant to physical functioning limitations in patients with CKD was developed using data from a targeted literature review (patients with CKD stages IV-V) and previous interviews (patients with CKD stages IIIa-IIIb). The preliminary conceptual model informed a semi-structured interview guide designed to capture experiences of physical functioning limitations in patients with CKD. Patients with CKD stages IV-V who were not receiving dialysis were interviewed; their responses were used to develop a comprehensive conceptual model summarizing their experiences associated with physical functioning limitations. RESULTS: A total of 25 patients with CKD stage IV (n = 19) or V (n = 6) were interviewed. Based on patient responses, the reported concepts were grouped into one of six categories: physical functioning limitations/difficulties, behavioural impacts, activity participation restrictions, symptoms attributed to physical functioning limitations, impacts on sleep and emotional functioning impacts related to physical functioning limitations. Twenty-three patients reported concepts associated with physical functioning limitations, most frequently 'walking up and down stairs' (83%) and 'walking distances' (74%). All 23 patients also reported behavioural impacts, including 'need to rest/subsequent periods of rest' (100%) and 'participation in fewer activities' (91%). As well as summarizing the reported concepts, the comprehensive conceptual model shows how concepts may relate to one another; for example, challenging symptoms or difficulty completing tasks can lead to changes in patient behaviour such as purposely reducing or avoiding activities. CONCLUSIONS: This study found that patients with late-stage CKD not receiving dialysis who experience physical functioning limitations report a range of impacts on their daily lives. The comprehensive conceptual model summarizes the concepts reported and the relationships between them, providing a holistic understanding of how patients with late-stage CKD are affected by physical functioning limitations. Infographic available for this article. INFOGRAPHIC.

Real-world walking cadence in people with COPD.

Introduction: The clinical validity of real-world walking cadence in people with COPD is unsettled. Our objective was to assess the levels, variability and association with clinically relevant COPD characteristics and outcomes of real-world walking cadence. Methods: We assessed walking cadence (steps per minute during walking bouts longer than 10 s) from 7 days' accelerometer data in 593 individuals with COPD from five European countries, and clinical and functional characteristics from validated questionnaires and standardised tests. Severe exacerbations during a 12-month follow-up were recorded from patient reports and medical registries. Results: Participants were mostly male (80%) and had mean±sd age of 68±8 years, post-bronchodilator forced expiratory volume in 1 s (FEV1) of 57±19% predicted and walked 6880±3926 steps·day-1. Mean walking cadence was 88±9 steps·min-1, followed a normal distribution and was highly stable within-person (intraclass correlation coefficient 0.92, 95% CI 0.90-0.93). After adjusting for age, sex, height and number of walking bouts in fractional polynomial or linear regressions, walking cadence was positively associated with FEV1, 6-min walk distance, physical activity (steps·day-1, time in moderate-to-vigorous physical activity, vector magnitude units, walking time, intensity during locomotion), physical activity experience and health-related quality of life and negatively associated with breathlessness and depression (all p<0.05). These associations remained after further adjustment for daily steps. In negative binomial regression adjusted for multiple confounders, walking cadence related to lower number of severe exacerbations during follow-up (incidence rate ratio 0.94 per step·min-1, 95% CI 0.91-0.99, p=0.009). Conclusions: Higher real-world walking cadence is associated with better COPD status and lower severe exacerbations risk, which makes it attractive as a future prognostic marker and clinical outcome.

Chronic Airways Assessment Test: psychometric properties in patients with asthma and/or COPD.

BACKGROUND: No short patient-reported outcome (PRO) instruments assess overall health status across different obstructive lung diseases. Thus, the wording of the introduction to the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) was modified to permit use in asthma and/or COPD. This tool is called the Chronic Airways Assessment Test (CAAT). METHODS: The psychometric properties of the CAAT were evaluated using baseline data from the NOVELTY study (NCT02760329) in patients with physician-assigned asthma, asthma + COPD or COPD. Analyses included exploratory/confirmatory factor analyses, differential item functioning and analysis of construct validity. Responses to the CAAT and CAT were compared in patients with asthma + COPD and those with COPD. RESULTS: CAAT items were internally consistent (Cronbach's alpha: > 0.7) within each diagnostic group (n = 510). Models for structural and measurement invariance were strong. Tests of differential item functioning showed small differences between asthma and COPD in individual items, but these were not consistent in direction and had minimal overall impact on the total score. The CAAT and CAT were highly consistent when assessed in all NOVELTY patients who completed both (N = 277, Pearson's correlation coefficient: 0.90). Like the CAT itself, CAAT scores correlated moderately (0.4-0.7) to strongly (> 0.7) with other PRO measures and weakly (< 0.4) with spirometry measures. CONCLUSIONS: CAAT scores appear to reflect the same health impairment across asthma and COPD, making the CAAT an appropriate PRO instrument for patients with asthma and/or COPD. Its brevity makes it suitable for use in clinical studies and routine clinical practice. TRIAL REGISTRATION: NCT02760329.

From Meaningful Outcomes to Meaningful Change Thresholds: A Path to Progress for Establishing Digital Endpoints.

This paper examines the use of digital endpoints (DEs) derived from digital health technologies (DHTs), focusing primarily on the specific considerations regarding the determination of meaningful change thresholds (MCT). Using DHTs in drug development is becoming more commonplace. There is general acceptance of the value of DHTs supporting patient-centric trial design, capturing data outside the traditional clinical trial setting, and generating DEs with the potential to be more sensitive to change than conventional assessments. However, the transition from exploratory endpoints to primary and secondary endpoints capable of supporting labeling claims requires these endpoints to be substantive with reproducible population-specific values. Meaningful change represents the amount of change in an endpoint measure perceived as important to patients and should be determined for each digital endpoint and given population under consideration. This paper examines existing approaches to determine meaningful change thresholds and explores examples of these methodologies and their use as part of DE development: emphasizing the importance of determining what aspects of health are important to patients and ensuring the DE captures these concepts of interest and aligns with the overarching endpoint strategy. Examples are drawn from published DE qualification documentation and responses to qualification submissions under review by the various regulatory authorities. It is the hope that these insights will inform and strengthen the development and validation of DEs as drug development tools, particularly for those new to the approaches to determine MCTs.

Muscle mass and quality as predictors for complications, recurrence and length of hospital stay in acute uncomplicated diverticulitis: a retrospective cohort study.

OBJECTIVES: The aim of this study was to investigate the potential correlation between muscle mass/muscle quality and risk of complications or recurrence in patients presenting with acute uncomplicated diverticulitis. It was also to study if low muscle mass/quality correlated to prolonged hospital stay. MATERIALS AND METHODS: The study population comprised 501 patients admitted to Helsingborg Hospital or Skåne University Hospital between 1 January 2015 and 31 December 2017, who had been diagnosed with acute uncomplicated diverticulitis and undergone computed tomography upon admission. The scans were used to estimate skeletal muscle mass and muscle radiation attenuation (an indicator for muscle quality). Skeletal muscle index was obtained by adjusting skeletal muscle mass to the patients' height. Values of below the fifth percentile of a normal population were considered low. RESULTS: There were no differences between the patients with normal versus those with low skeletal muscle mass, skeletal muscle index or muscle radiation attenuation regarding risk of complications or recurrence of diverticular disease. However, as only 11 patients had complications, no conclusion as to a potential correlation can be made. Low muscle quality correlated to longer hospital stay, also when adjusting for other potential confounders. CONCLUSIONS: Muscle mass/quality do not seem to serve as predictor of risk for recurrent disease in patients with acute uncomplicated diverticulitis. However, low muscle radiation attenuation was associated with prolonged hospital stay. This indicates that muscle quality, assessed by computed tomography scan, might be used in clinical practise to identify patients at risk of longer hospitalisation.

Physical activity end-points in trials of chronic respiratory diseases: summary of evidence.

Background: Physical activity contributes to improving respiratory symptoms. However, validated end-points are few, and there is limited consensus about what is a clinically meaningful improvement for patients. This review summarises the evidence to date on the range of physical activity end-points used in COPD, asthma and idiopathic pulmonary fibrosis (IPF) whilst evaluating their appropriateness as end-points in trials and their relation to patients' everyday life. Methods: Trials reporting physical activity end-points were collected using Citeline's database Trialtrove; this was supplemented by searches in PubMed. Results: The daily-patient-reported outcome (PRO)active and clinical visit-PROactive physical activity composite end-points appeared superior at capturing the full experience of physical activity in patients with COPD and were responsive to bronchodilator intervention. Time spent in moderate-to-vigorous physical activity is a recently validated end-point for IPF that correlates with exercise capacity and quality of life. Step count appears the best available physical activity measure for asthma, which consistently declines with worse disease status. However, evidence suggests a time lag before significant improvement in step count is seen which may reflect the impact of human behaviour on physical activity. Conclusions: Physical activity represents a challenging domain to accurately measure. This is the first review evaluating physical activity measures used specifically within the respiratory field. Whilst physical activity can be effectively captured using PROactive in patients with COPD, this review highlights the unmet need for novel patient-focused end-points in asthma and IPF which would offer opportunities to develop efficacious medicines with impact on patients' therapeutic care and quality of life.

Objectively Measured Physical Activity in Patients with COPD: Recommendations from an International Task Force on Physical Activity.

Physical activity (PA) is of key importance for health among healthy persons and individuals with chronic obstructive pulmonary disease (COPD). PA has multiple dimensions that can be assessed and quantified objectively using activity monitors. Moreover, as shown in the published literature, variable methodologies have been used to date to quantify PA among individuals with COPD, precluding clear comparisons of outcomes across studies. The present paper aims to provide a summary of the available literature for the rationale behind using objectively measured PA and proposes a standardized methodology for assessment, including standard operating procedures for future research. The present paper, therefore, describes the concept of PA, reports on the importance of PA, summarizes the dimensions of PA, provides a standard operating procedure on how to monitor PA using objective assessments, and describes the psychometric properties of objectively measured PA. The present international task force recommends implementation of the standard operating procedure for PA data collection and reporting in the future. This should further clarify the relationship between PA and clinical outcomes, test the impact of treatment interventions on PA in individuals with COPD, and successfully propose a PA endpoint for regulatory qualification in the future.

Development of a preliminary conceptual model of the patient experience of chronic kidney disease: a targeted literature review and analysis.

BACKGROUND: Patient-reported outcome (PRO) instruments should capture the experiences of disease and treatment that patients consider most important in order to inform patient-centred care and product development. The aim of this study was to develop a preliminary conceptual model of patient experience in chronic kidney disease (CKD) based on a targeted literature review and to characterize existing PRO instruments used in CKD. METHODS: PubMed, EMBASE and Cochrane databases and recent society meetings were searched for publications reporting signs/symptoms and life impacts of CKD. Concepts identified in the literature review were used to develop a preliminary conceptual model of patient experience of CKD, overall, and within patient subpopulations of differing CKD causes, severities and complications. PRO instruments, identified from PRO databases, CKD literature and CKD clinical trials, were assessed for content validity, psychometric strength and coverage of concepts in the literature review. RESULTS: In total, 100 publications met criteria for analysis; 56 signs/symptoms and 37 life impacts of CKD were identified from these sources. The most frequently mentioned signs/symptoms were pain/discomfort (57% of publications) and tiredness/low energy/lethargy/fatigue (42%); the most commonly reported life impacts were anxiety/depression (49%) and decrements in physical functioning (43%). Signs/symptoms and life impacts varied across the subpopulations and were more frequent at advanced CKD stages. The preliminary conceptual model grouped signs/symptoms into seven domains (pain/discomfort; energy/fatigue; sleep-related; gastrointestinal-related; urinary-related; skin-/hair-/nails-related; and other) and life impacts into six domains (psychological/emotional strain; cognitive impairment; dietary habit disruption; physical function decrements; interference with social relationships; and other). Eleven PRO instruments were considered to be promising for use in CKD; all had limitations. CONCLUSIONS: Although preliminary, the proposed conceptual model highlights key PROs for people with CKD and is intended to spur development of more tailored PRO instruments to assess these concepts.

Heterogeneity within and between physician-diagnosed asthma and/or COPD: NOVELTY cohort.

BACKGROUND: Studies of asthma and chronic obstructive pulmonary disease (COPD) typically focus on these diagnoses separately, limiting understanding of disease mechanisms and treatment options. NOVELTY is a global, 3-year, prospective observational study of patients with asthma and/or COPD from real-world clinical practice. We investigated heterogeneity and overlap by diagnosis and severity in this cohort. METHODS: Patients with physician-assigned asthma, COPD or both (asthma+COPD) were enrolled, and stratified by diagnosis and severity. Baseline characteristics were reported descriptively by physician-assigned diagnosis and/or severity. Factors associated with physician-assessed severity were evaluated using ordinal logistic regression analysis. RESULTS: Of 11 243 patients, 5940 (52.8%) had physician-assigned asthma, 1396 (12.4%) had asthma+COPD and 3907 (34.8%) had COPD; almost half were from primary care. Symptoms, health-related quality of life and spirometry showed substantial heterogeneity and overlap between asthma, asthma+COPD and COPD, with 23%, 62% and 64% of patients, respectively, having a ratio of post-bronchodilator forced expiratory volume in 1 s to forced vital capacity below the lower limit of normal. Symptoms and exacerbations increased with greater physician-assessed severity and were higher in asthma+COPD. However, 24.3% with mild asthma and 20.4% with mild COPD had experienced ≥1 exacerbation in the past 12 months. Medication records suggested both under-treatment and over-treatment relative to severity. Blood eosinophil counts varied little across diagnosis and severity groups, but blood neutrophil counts increased with severity across all diagnoses. CONCLUSION: This analysis demonstrates marked heterogeneity within, and overlap between, physician-assigned diagnosis and severity groups in patients with asthma and/or COPD. Current diagnostic and severity classifications in clinical practice poorly differentiate between clinical phenotypes that may have specific risks and treatment implications.

Validation of a diagnosis-agnostic symptom questionnaire for asthma and/or COPD.

Background: The Respiratory Symptoms Questionnaire (RSQ) is a novel, four-item patient-reported diagnosis-agnostic tool designed to assess the frequency of respiratory symptoms and their impact on activity, without specifying a particular diagnosis. Our objective was to examine its validity in patients with asthma and/or chronic obstructive pulmonary disease (COPD). Methods: Baseline data were randomly sampled from patients who completed the RSQ in the NOVELTY study (ClinicalTrials.gov: NCT02760329). The total sample (n=1530) comprised three randomly selected samples (n=510 each) from each physician-assigned diagnostic group (asthma, asthma+COPD and COPD). The internal consistency and structural validity of the RSQ were evaluated using exploratory and confirmatory factor analyses; psychometric performance was observed using Classical Test Theory and Item Response Theory analyses. Results: For the total sample, the mean±sd RSQ score was 5.6±4.3 (range 0-16). Irrespective of diagnosis, the internal consistency of items was uniformly adequate (Cronbach's α=0.76-0.80). All items had high factor loadings and structural characteristics of the measure were invariant across groups. Using the total sample, RSQ items informatively covered the θ score range of -2.0 to 2.8, with discrimination coefficients for individual items being high to very high (1.7-2.6). Strong convergent correlations were observed between the RSQ and the St George's Respiratory Questionnaire (0.77, p<0.001). Conclusions: The RSQ is a valid, brief, patient-reported tool for assessing respiratory symptoms in patients across the whole spectrum of asthma and/or COPD, rather than using different questionnaires for each diagnosis. It can be used for monitoring respiratory symptoms in clinical practice, clinical trials and real-world studies.

Validity and responsiveness of the Daily- and Clinical visit-PROactive Physical Activity in COPD (D-PPAC and C-PPAC) instruments.

BACKGROUND: The Daily-PROactive and Clinical visit-PROactive Physical Activity (D-PPAC and C-PPAC) instruments in chronic obstructive pulmonary disease (COPD) combines questionnaire with activity monitor data to measure patients' experience of physical activity. Their amount, difficulty and total scores range from 0 (worst) to 100 (best) but require further psychometric evaluation. OBJECTIVE: To test reliability, validity and responsiveness, and to define minimal important difference (MID), of the D-PPAC and C-PPAC instruments, in a large population of patients with stable COPD from diverse severities, settings and countries. METHODS: We used data from seven randomised controlled trials to evaluate D-PPAC and C-PPAC internal consistency and construct validity by sex, age groups, COPD severity, country and language as well as responsiveness to interventions, ability to detect change and MID. RESULTS: We included 1324 patients (mean (SD) age 66 (8) years, forced expiratory volume in 1 s 55 (17)% predicted). Scores covered almost the full range from 0 to 100, showed strong internal consistency after stratification and correlated as a priori hypothesised with dyspnoea, health-related quality of life and exercise capacity. Difficulty scores improved after pharmacological treatment and pulmonary rehabilitation, while amount scores improved after behavioural physical activity interventions. All scores were responsive to changes in self-reported physical activity experience (both worsening and improvement) and to the occurrence of COPD exacerbations during follow-up. The MID was estimated to 6 for amount and difficulty scores and 4 for total score. CONCLUSIONS: The D-PPAC and C-PPAC instruments are reliable and valid across diverse COPD populations and responsive to pharmacological and non-pharmacological interventions and changes in clinically relevant variables.

Could 30 years of political controversy on needle exchange programmes in Sweden contribute to scaling-up harm reduction services in the world?

Aims: To end the hepatitis and AIDS epidemics in the world by 2030, countries are encouraged to scale-up harm reduction services and target people who inject drugs (PWID). Blood-borne viruses (BBV) among PWID spread via unsterile injection equipment sharing and to combat this, many countries have introduced needle and syringe exchange programmes (NEP), though not without controversy. Sweden's long, complicated harm reduction policy transition has been deviant compared to the Nordic countries. After launch in 1986, no NEP were started in Sweden for 23 years, the reasons for which are analysed in this study. Methods: Policy documents, grey literature and research mainly published in 2000-2017 were collected and analysed using a hierarchical framework, to understand how continuous build-up of evidence, decisions and key events, over time influenced NEP development. Results: Sweden's first NEP opened in a repressive-control drug policy era with a drug-free society goal. Despite high prevalence of BBV among PWID with recurring outbreaks, growing research and key-actor support including a NEP law, no NEP were launched. Political disagreements, fluctuating actor-coalitions, questioning of research, and a municipality veto against NEP, played critical roles. With an individual-centred perspective being brought into the drug policy domain, the manifestation of a dual drug and health policy track, a revised NEP law in 2017 and removal of the veto, Sweden would see fast expansion of new NEP. Conclusions: Lessons from the Swedish case could provide valuable insight for countries about to scale-up harm reduction services including how to circumvent costly time- and resource-intensive obstacles and processes involving ideological and individual moral dimensions.

Treatment of age-related macular degeneration after cataract surgery: a study from the Swedish National Cataract and Macula Registers.

PURPOSE: To characterize pre- and perioperative factors associated with treatment for wet age-related macular degeneration (wet AMD) after cataract surgery. METHODS: This register-based cohort study with data from the Swedish National Cataract Register (NCR) and the Swedish Macula Register (SMR) from 2010 to 2017 compared eyes with and without preoperative AMD that had undergone cataract surgery and was subsequently treated for wet AMD to eyes not treated within the study period. All first-eye surgeries registered in the NCR from 2010 to 2017 and matching eyes found in the SMR that had undergone treatment for wet AMD ≥ 1 year after the cataract procedure were included. Data for cataract surgery date, age and gender, use of a blue-blocking IOL, preoperative visual acuity, ocular comorbidities, posterior capsule rupture and date of AMD treatment initiation were extracted. RESULTS: The only independent factor associated with postoperative treatment of wet AMD in both groups was female gender (67.3% vs. 58.8%, p < 0.001 and 66.4% vs. 60.6%, p = 0.001, respectively). Older age was an independent factor in eyes without preoperative AMD (78.4 ± 6.5 vs. 73.4 ± 9.6 years, p < 0.001). A blue-blocking IOL appeared to decrease the likelihood of subsequent wet AMD treatment slightly but not statistically significant in eyes with preoperative AMD (52.7% vs. 56.8%, p = 0.110). CONCLUSIONS: Some factors (female gender, high age) are associated with undergoing subsequent treatment for wet AMD to a higher extent. If the use of a blue-blocking IOL offers any protection from undergoing AMD treatment after cataract surgery, such an effect must be very small.

Computed Tomography Verified Prevalence of Incisional Hernia 1 Year Postoperatively after Colorectal Cancer Resection.

BACKGROUND AND OBJECTIVE: Incisional hernia is a frequent negative outcome after open and minimal invasive surgery of colorectal cancer. This study aimed to determine computed tomography-verified incisional hernia prevalence 1-year post colorectal cancer surgical resection in patients sutured with standardized small stich 4:1 technique, identify risk factors for incisional hernia and assess to what extent incisional hernia required surgical correction. METHODS: All patients subjected to resectional colorectal cancer surgery during 2012-2016 at Skåne University Hospital were identified in the Swedish Colorectal Cancer Registry. The 1-year follow-up computed tomography was re-evaluated to establish the presence of incisional hernia. Clinical data were collected from Swedish Colorectal Cancer Registry and the patients' medical charts were reviewed. Non-parametric tests and binary logistic regression analysis were used for statistical analysis. RESULTS: In total, 1744 tumors were identified resulting in 1231 patients meeting the inclusion criteria. In total, 25.9% (n = 319) had incisional hernia at the 1-year follow-up computed tomography and 13.2% (n = 162) of the colorectal cancer resections were minimal invasive surgery, and there was non-significant incisional hernia prevalence difference between open and minimal invasive surgery. However, for converted and non-converted minimal invasive surgery, the incisional hernia frequencies were 43.9% (n = 18) and 24.1% (n = 39), respectively (p = 0.012). Significant risk factors for incisional hernia were body mass index, wound rupture, and procedure time. During the follow-up time, 14.1% (n = 45) needed incisional hernia corrective surgery. CONCLUSIONS: Incisional hernia after colorectal cancer surgery is common despite standardized small stich 4:1 closure, but few incisional hernias are surgically corrected. Incisional hernia is equally frequent after open surgery and minimal invasive surgery. However, the risk of incisional hernia is considerably higher after minimal invasive surgery conversion.

A prospective cohort study of risk behaviours, retention and loss to follow-up over 5 years among women and men in a needle exchange program in Stockholm, Sweden.

BACKGROUND: Needle exchange programs (NEP) are important in reducing risk behaviours among people who inject drugs (PWID), also exposed to HIV and hepatitis C (HCV) through injecting drug use (IDU). Women (WWID) compared to men who inject drugs (MWID), are particularly vulnerable with complex needs, however less is known about their risk determinants and NEP outcomes. METHODS: In an open prospective NEP cohort, 697 WWID and 2122 MWID were followed, 2013-2018. Self-reported socio/drug-related determinants for receptive injection (needle/syringe and paraphernalia) and sexual risk behaviours at enrolment, lost to follow-up (LTFU) and probability of retention, were assessed for both groups. Multivariable logistic regression (adjusted odds ratios, aOR) for enrolment and Poisson regression (adjusted incidence rate ratios, aIRR) for LTFU, were used. Cumulative NEP-retention probability was analysed using a six- and 12-month scenario. RESULTS: At NEP enrolment, injection risk behaviours among WWID were associated with: younger age; homelessness; amphetamine-IDU; non-participation in opioid substitution therapy (OST); history of custody and among MWID: lower education level; cohabitation; homelessness, being a tenant; amphetamine-IDU; non-participation in OST; history of being sectioned, HIV-negative and HCV-positive. Condomless sex among WWID was associated with: younger age; lower education-level; cohabitation; having a partner; amphetamine-IDU; non-participation in OST; being HIV-negative and HCV-positive and among MWID: younger age; married; cohabitation; having a partner; amphetamine-IDU; non-participation in OST; history of custody, prison and being HIV-negative. WWID had higher NEP-retention levels compared to MWID over time. Being LTFU among WWID was associated with being HIV-negative and reporting injection risk behaviours and among MWID, younger age, non-participation in OST, being HIV-negative and having protected sex. CONCLUSIONS: Despite better NEP compliance among WWID, high injection and sexual risk behaviours in both gender-subgroups, especially in intimate relationships, suggests ongoing HCV and HIV-infection risks. Subgroup-variation in the NEP continuum of care warrants more gender-disaggregated research and tailoring gender-sensitive services may improve prevention, health and retention outcomes.

The greenhouse gas emission effects of rewetting drained peatlands and growing wetland plants for biogas fuel production.

Efforts to mitigate greenhouse gas (GHG) emissions are receiving increased attention among governmental and commercial actors. In recent years, the interest in paludiculture, i.e. the use of rewetted peatlands, has grown because of its potential to reduce GHG emissions by stopping soil decomposition. Moreover, cultivating wetland plants on rewetted peatlands for bioenergy production that replaces fossil fuels in the transport sector, can contribute to additional GHG emission reductions. In this study, an analysis of literature data was conducted to obtain data on GHG emissions (CO2 and CH4) and biomass production from rewetted peatlands cultivated with two different wetland plant species: Phragmites australis (Pa) and Typha latifolia (Tl). In addition, a biogas experiment was carried out to investigate the biomethane yield of Pa and Tl biomass, and the reduction of global warming potential (GWP) by using biomethane as vehicle fuel. The results show that peatland rewetting can be an important measure to mitigate the GWP as it reduces GHG emissions from the soil, particularly on a 100-year timescale but also to some extent on a 20-year timescale. More specifically, rewetting of 1 km2 of peatland can result in a GWP reduction corresponding to the emissions from ±2600 average sized petrol cars annually. Growing Pa on rewetted peatlands reduces soil GHG emissions more than growing Tl, but Pa and Tl produced similar amounts of biomass and biomethane per land area. Our study concludes that Pa, because of a more pronounced GWP reduction, is the most suitable wetland plant to cultivate after peatland rewetting.

Patterns of Physical Activity Progression in Patients With COPD.

INTRODUCTION: Although mean physical activity in COPD patients declines by 400-500steps/day annually, it is unknown whether the natural progression is the same for all patients. We aimed to identify distinct physical activity progression patterns using a hypothesis-free approach and to assess their determinants. METHODS: We pooled data from two cohorts (usual care arm of Urban Training [NCT01897298] and PROactive initial validation [NCT01388218] studies) measuring physical activity at baseline and 12 months (Dynaport MoveMonitor). We identified clusters (patterns) of physical activity progression (based on levels and changes of steps/day) using k-means, and compared baseline sociodemographic, interpersonal, environmental, clinical and psychological characteristics across patterns. RESULTS: In 291 COPD patients (mean±SD 68±8 years, 81% male, FEV1 59±19%pred) we identified three distinct physical activity progression patterns: Inactive (n=173 [59%], baseline: 4621±1757 steps/day, 12-month change (Δ): -487±1201 steps/day), ActiveImprovers (n=49 [17%], baseline: 7727±3275 steps/day, Δ:+3378±2203 steps/day) and ActiveDecliners (n=69 [24%], baseline: 11 267±3009 steps/day, Δ: -2217±2085 steps/day). After adjustment in a mixed multinomial logistic regression model using Active Decliners as reference pattern, a lower 6-min walking distance (RRR [95% CI] 0.94 [0.90-0.98] per 10m, P=.001) and a higher mMRC dyspnea score (1.71 [1.12-2.60] per 1 point, P=.012) were independently related with being Inactive. No baseline variable was independently associated with being an Active Improver. CONCLUSIONS: The natural progression in physical activity over time in COPD patients is heterogeneous. While Inactive patients relate to worse scores for clinical COPD characteristics, Active Improvers and Decliners cannot be predicted at baseline.

Using interviews and observations in clinical practice to enhance authenticity in virtual patients for interprofessional education.

BACKGROUND: Interprofessional collaboration is increasingly important in healthcare, but interprofessional education (IPE) faces challenges, such as different study programmes with varied schedules and campuses. These challenges can be met, in part, by using web-based virtual patients (VPs) as a tool in IPE. However, demands for relevant patient presentations and clinical practice increase when VPs are used by students from different programmes. The aim of this study was to improve the presentation of professional perspectives regarding nurses and physicians and their collaboration in order to increase the clinical authenticity of existing VPs. METHODS: Clinical observations were conducted to gain familiarity with the context. Semi-structured interviews were performed with individual nurses and physicians with experience of patients with leg ulcers. The interviews were recorded, transcribed and analysed using thematic analysis. RESULTS: The clinical observations exposed a lack of interprofessional collaboration in practice with regard to patients with leg ulcers. The interview analysis resulted in two themes: Clinical care and Organizational structure. The theme Clinical care included nursing with a holistic approach to the patient and awareness of the patient's well-being, including nutrition and home situation. The theme Organizational structure revealed a lack of teamwork in primary care. The interviewees stressed learning together and sharing responsibility, and they emphasised the importance of implementing interprofessional learning in the education of nurses and physicians in order to stimulate future teamwork. The VP should offer a broad medical history so that healthcare students are made aware of how a disease can affect the patient's social situation, and thereby illustrate the importance of interprofessional collaboration. The information should also be comprehensive and clear, leading to a diagnosis, so the student can gain clinical knowledge and build a foundation for discussion of treatment. CONCLUSIONS: Interviews and observations in clinical practice can be used to enhance authenticity in VPs for interprofessional learning. A thorough look at authentic clinical environments can enrich and improve educational settings using VPs, and it can highlight the challenges students can encounter in clinical care of the patient and in an organisation with regard to interprofessional collaboration.

A qualitative study of facilitators and barriers to participate in a needle exchange program for women who inject drugs.

BACKGROUND: Women who inject drugs (WWID) show higher levels of injecting risk behaviour compared to men, putting them at risk of contracting HIV and hepatitis C (HCV). Compared to men, WWID are also less present in harm reduction programs such as needle exchange programs (NEP). The aim of this study is to investigate reasons for, and barriers to, participation in NEP among WWID in Sweden, and to identify measures that could be taken to strengthen the program and increase participation among WWID. METHOD: In-depth interviews (IDIs) were conducted with 20 WWID who had participated in the Stockholm NEP for at least six months and was over 18 years old. IDIs were audio recorded and transcribed et verbatim. Qualitative content analysis was used to identify themes. RESULTS: The need for sterile injection equipment was identified as the main driver to join and remain in the NEP program. Continuous participation in the NEP was further driven by easy access to a multitude of health-related services. The most valued service was the sexual and reproductive health services (SRHR), allowing participants to access contraceptives, cervical cancer screening and sexually transmitted infections testing (STI-testing). NEP staffs' respectful treatment of participants further contributed to program participation. However, participants also expressed a number of concerns around NEP participation, which created barriers to joining. These included losing custody or visitation rights to children, male partner jealousy and violence, unwillingness to spend time in the waiting area and fear of receiving positive HIV/HCV test results. Practical barriers included limited opening hours and travel distance to the NEP. To strengthen the program, most participants requested additional SRHR services. Most participants also proposed some form of "women only" access to the NEP, to strengthen the feeling of the NEP as a safe space. CONCLUSION: This study identified factors that may increase uptake of NEP among WWID. Additional SRHR services and "women only" access are recommended to be implemented and evaluated as part of NEP. These findings may inform and improve the current scale-up of NEPs in Sweden to ensure equal access to services.

COPDCompEx: A novel composite endpoint for COPD exacerbations to enable faster clinical development.

BACKGROUND: Frequency of moderate and severe chronic obstructive pulmonary disease exacerbations is an important endpoint in clinical trials, but makes them large and lengthy when powered to evaluate it. We aimed to develop a composite endpoint (COPDCompEx) that could predict treatment effect on exacerbations, enabling the design of shorter early phase clinical trials requiring fewer patients. METHODS: In this post hoc analysis, data from 20 randomized controlled trials were used to develop and test COPDCompEx. Diary events were tested against predefined threshold values for peak expiratory flow, reliever medication use, and symptoms. A COPDCompEx event was defined as first occurrence of a diary event, a moderate or severe exacerbation, or a study dropout. Ratios of event frequency, treatment effect and future trial sample size were compared between COPDCompEx and moderate and severe exacerbations. FINDINGS: At 3 months, the proportion of patients experiencing COPDCompEx events increased over 3-fold versus exacerbations alone. All components contributed to COPDCompEx event rate. Treatment effects at 3 months were closely matched between COPDCompEx and exacerbations, and the large net gain in power substantially reduced the required sample size. INTERPRETATION: COPDCompEx may be used to predict treatment effect on moderate and severe exacerbations of chronic obstructive pulmonary disease. This may enable the design of shorter Phase 2 clinical trials requiring fewer patients when compared with current exacerbation studies, with exacerbations as a key Phase 3 endpoint. This would, therefore, allow more efficient decision-making with reduced burden and risk to study participants.